Resorcinol and its derivatives have a wide variety of applications. The largest consumption of resorcinol is in the tyre industry where the preferred hardening resins are based on resorcinol. Another value-added application of resorcinol and its derivatives is in cosmetic products. Some compounds like 2,4-dihydroxyacetophenone have been used in sun-protective applications or compositions for providing sun protection.
Alkyl and aryl resorcinols are reported to possess valuable therapeutic and antiseptic properties. In particular, 4-alkyl resorcinols are reported to have skin-beautifying effect and low toxicity and irritation when applied on to human skin. Alkyl resorcinols like 4-n-butyl resorcinol have been used in skin creams and lotions which are claimed to have good bleaching and anti-microbial effect. 2-alkyl resorcinols (where the alkyl group is linear) have been reported to have skin depigmentation properties.
Synthetic Communications 15 (14), 1315-24 (1985) describes a process to prepare 4-ethyl resorcinol by reaction of 2,4-dihydroxy acetophenone and sodium borocyano hydride in methanol medium. This process is difficult to implement on industrial scale and not cost-effective as sodium boro cyano hydride is not a catalyst but one of the reactants and so the reaction produces a lot of by products which are difficult to dispose off in an environmentally safe way.
There are many publications on the use of zinc and mercuric compounds to prepare compounds of formula I starting with compounds of formula II. J. Am Chem. Soc., 52, 4866-82 (1930) reports a process where 4-ethyl resorcinol has been prepared in 82% yield by reaction of 2,4-dihydroxy acetophenone with Zn and mercuric chloride in hydrochloric acid solution. Rec. trav. Chim. 50, 848-50 (1931) describes preparation of compound of formula I where R is a strain chain alkyl group with a carbon chain length of 5 in 84% yield by reaction of the corresponding ketone in the presence of Zn and dilute hydrochloric acid. The same product has been reported to be prepared in 71% yield in Acad. Rep. Populare Romine. Studii cercetari chim., 3, 13-18 (1955) by using Zn and mercuric chloride as the catalysts. The above methods are industrially not viable as the process comprises use of toxic and environmentally unfriendly chemicals containing mercury which are difficult to dispose off.
Tr. Tallin. Politekhn. In-ta (543) 78-83 (1983) reports the preparation of 4-ethyl resorcinol from 2,4-dihydroxyacetophenone in the presence of hydrochloric acid which is a non-catalytic reaction. The maximum yield reported is only 42% and therefore is not industrially workable.
Australian Journal of Chemistry, 22(3), 601-5 (1969) describes the preparation of 4-ethyl resorcinol by reaction of 2,4-dihydroxyacetophenone with sodium borohydride which is a non-catalytic reaction. This reaction is not an industrially feasible reaction due to the large amount of sodium borohydride that needs to be used and the problems of downstream purification.
Compound of formula I, but with a much higher carbon chain length of 14 has been reported in Journal of Medicinal Chemistry 29 (5), 606-11 (1986) to be prepared by the reaction of the corresponding compound of formula II with hydrogen gas and acetic acid using palladium as the catalyst in ethanol medium. This reaction produces the desired product with poor yield and the rate of reaction becomes increasingly slower with time.
J. Am Chem. Soc. (1939), 61, 249-54 describes that reduction of dihydroxy acetophenone with a palladium catalyst gave only a poor yield of 4-ethyl resorcinol and so the study was not extended.
There is thus a need felt in the art to develop a process to prepare compounds of formula I in high yields and purity, which can therefore be an industrially viable process. The present inventors have found that compounds of formula I can be prepared in very high yields and purity by reacting compounds of formula II with a source of hydrogen in the presence of a mixture of at least two catalysts chosen from Nickel, Raney Nickel and Palladium.